Glucose concentration regulates the synthesis of insulin in pancreatic islets. We are studying the molecular mechanisms underlying this regulation, primarily at the mRNA level using both insulinoma cell lines and isolated pancreatic islets. We are in the process of developing cell conditions which will support the response of insulin synthesis to various stimuli. Preliminary results on stimulation of insulin synthesis by glucose indicate that while total amounts of cytoplasmic insulin RNA remain constant, there is an alteration in the size of these transcripts in response to changes in glucose levels. We are currently attempting to characterize the structural differences between these messages. In collaboration with L. Reid at Albert Einstein College of Medicine, we have demonstrated an approximately ten-fold increase in insulin-specific mRNA in rat insulinoma cells grown on extracellular matrix and serum-free medium as compared to cells grown on the usual tissue culture substrate in serum containing medium.